Safety and Biomarker of OPB-111077 in Subjects With Advanced Solid Tumor

A Phase 1, Open-label, Non-Randomized, Dose Escalation Trial to Evaluate Safety and Biomarker of OPB-111077 in Subjects With Advanced Solid Tumor

This open-label, non-randomized trial will comprise of 2 parts. A dose escalation part will characterize the safety, biomarker and pharmacokinetics of OPB-111077 in advanced solid tumor. Subsequently, an expansion part will further evaluate the biomarker, safety, pharmacokinetics and antitumor activity of OPB-111077 in selected tumor types.

Study Overview

• Status: Completed
• Conditions: Solid Tumor
• Intervention / Treatment: Drug: OPB-111077

Detailed Description

This trial is designed to determine the safety, tolerability, maximum tolerated dose and recommended dose of OPB-111077 administered orally 4-days on and 3-days off (3 weeks/cycle) to subjects with advanced solid tumor in the dose escalation part so that biomarkers, efficacy, and others can be evaluated at the recommended dose in an expeditious manner in the expansion part. The dose escalation part employs a 3+3 escalation design as a standard dose escalation design for a small sample size.

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Seoul National University Hospital
  • Seoul, Korea, Republic of
    • Asan Medical Center
  • Seoul, Korea, Republic of
    • Seoul National University Bundang Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Pathologically and/or cytologically confirmed advanced solid tumor
2. Patients who were refractory to standard therapy or for which there are no standard treatment options available
3. Age 20 to 80 years at the time of informed consent
4. Patients who, together with their partner, are willing and capable of using an appropriate method of contraception throughout the trial period and until at least 12 weeks after final IMP administration
5. Patients informed of the diagnosis of advanced solid tumor who are fully informed about the content of the study by the investigator or subinvestigator using the specified written consent form and other written explanation, and give written consent to participate in the study of their free will
6. Patients who are able to take oral medication

Exclusion Criteria:

1. Patients with symptomatic brain metastases
2. Patients who have not recovered from any prior therapy related toxicity deemed to be clinically significant at study entry, except for the test item defined in inclusion criteria.
3. Patients with active infections needing whole body therapy
4. Patients with positive hepatitis B surface (HBs) antigen or positive hepatitis C virus (HCV) antibody
5. Patients with positive human immunodeficiency virus (HIV) antibody
6. Patients with uncontrollable cardiac diseases
7. Patients with uncontrollable pain by analgesic drugs
8. Patients with a history of organ transplantation
9. Patients who have received another IMP
10. Patients who are pregnant, possibly pregnant, or lactating
11. Patients otherwise judged by the investigator or subinvestigator to be inappropriate for inclusion in the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OPB-111077; Tablet, Oral, 300mg/500mg/700mg/900mg 4 days-on & 3 days-off (21 days=1cycle)	Drug: OPB-111077; Tablet, Oral, 300mg/500mg/700mg/900mg 4 days-on & 3 days-off (21 days=1cycle)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Number of participants with Adverse Events	21 days
Maximum tolerated dose	The highest dose that does not lead to discontinuation of dose escalation	21 days
Biomarker of OPB-111077	Change from baseline on predictable biomarker specified in the protocol	21 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor response measured by RECIST(Response Evaluation Criteria in Solid Tumor) 1.1 Assessment	Tumor response measured by RECIST(Response Evaluation Criteria in Solid Tumor) 1.1 Assessment will be conducted at Screening, end of Cycle 1, end of Cycle 2, end of every 2 cycles thereafter, at the final study visit.	3~18 weeks depending on tumor response
Pharmacokinetics (PK) properties of OPB-111077 and its metabolites.	The following PK parameters (Cmax (maximum observed concentration), AUC(area uder the concentration time curve from zero), tmax (Time to maximum plasma concentration), etc.) will be determined using a non-compartmental methods.	21 days

Collaborators and Investigators

• Sponsor: Korea Otsuka Pharmaceutical Co., Ltd.
• Collaborators: Otsuka Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Doyoun Oh, MD, Seoul National University Hospital; Principal Investigator: Jeehyun Kim, MD, Seoul National University Bundang Hospital; Principal Investigator: Sungbae Kim, MD, Asan Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2014
• Primary Completion (Actual): March 8, 2019
• Study Completion (Actual): March 8, 2019

Study Registration Dates

• First Submitted: September 23, 2014
• First Submitted That Met QC Criteria: September 24, 2014
• First Posted (Estimate): September 26, 2014

Study Record Updates

• Last Update Posted (Actual): September 10, 2019
• Last Update Submitted That Met QC Criteria: September 9, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: 317-KOA-1401i